Vir成为生物技术泡沫海报的孩子

StephenW

Vir becomes a biotech bubble poster child

    Jacob Plieth

The company surges 74% though its hints of clinical activity concern just six hep B patients and could include those on placebo.
Trial Results
A bubble.

An initial report of clinical activity against hepatitis B that can at best be said to support proof of concept – and including placebo as well as active cohort subjects – yesterday caused a $4bn valuation uplift. Welcome to biotech investing in 2021.

The company in question is the virology group Vir Biotechnology, which until now had ridden a wave of investor enthusiasm largely owing to its work in Covid-19. No matter, Vir is now capitalised at almost $10bn, a market reaction implying that at least some are convinced that it could be on the way to curing the coronavirus and hep B alike.

Clearly this is far from proven. Yesterday’s brief update concerned the first findings from a blinded, placebo-controlled clinical trial of VIR-3434, a monoclonal antibody approach to treating hep B, and came nine months after Vir reported clinical data with VIR-2218, a separate siRNA approach (Vir bids to enter the hepatitis B race, April 16, 2020).

Blinded

The VIR-3434 study remains blinded, so whether anything Vir disclosed yesterday is relevant is up for debate.

Specifically, the company says six of the eight subjects randomised so far have achieved a mean day-eight reduction of 1.3 log10 IU/ml in HBsAg, the surface antigen that is one of four major hep B transcripts the virus is believed to use to replicate and rebound.

Coincidentally six patients have so far been assigned to VIR-3434 and two to placebo, so the strong hint is that these six are the same six who achieved the HBsAg decline cited. But there is absolutely no evidence that this is the case, as the trial has not been unblinded.

At the very least investors should wait to see the other two subjects’ HBsAg levels, even before considering whether HBsAg is a relevant biomarker, and even whether chronic hep B, which mostly occurs in developing countries, is a viable market. To achieve a functional cure viral DNA and HBsAg must both be suppressed to prevent rebounds, and the virus also persists in a reservoir of cccDNA.

Relevance?

As for the relevance of HBsAg reduction at day eight in the VIR-3434 trial, according to clinicaltrials.gov the last of 16 secondary endpoints listed in the study concerns maximum serum HBsAg reduction from baseline between days 1 and 280.

But all Vir seems to have reported yesterday is the six most impressive HBsAg declines from blinded, blended data points of each of the eight subjects’ levels over time, averaged out to find a mean value.

True, the company says preclinical data had led it to believe that much higher VIR-3434 doses than the 6mg tested so far might be needed to achieve the level of HBsAg knockdown that it has reported in the six selected subjects.

But without knowing specifically how patients given VIR-3434 did versus those on placebo these initial findings seem meaningless. Caveat emptor.

StephenW

Vir成为生物技术泡沫海报的孩子

    雅各布·普利思

尽管其临床活动的提示仅涉及六名乙肝患者，并且可能包括安慰剂患者，但该公司股价飙升了74％。
试验结果
泡沫。

昨天，一份关于乙型肝炎的临床活动的初步报告充其量可以说是支持概念验证的报告，其中包括安慰剂以及活跃的队列研究对象，这些报告引起了40亿美元的估值提升。欢迎来到2021年的生物技术投资。

有问题的公司是病毒学集团Vir Biotechnology，迄今为止，该公司引起了投资者的热潮，这在很大程度上归功于其在Covid-19中的工作。不管如何，Vir现在的市值接近100亿美元，这是市场反应，表明至少有一些人确信Vir可能正在治愈冠状病毒和乙肝病毒。

显然，这还远未得到证实。昨天的简短更新涉及一项关于VIR-3434的盲法，安慰剂对照临床试验的第一个发现，VIR-3434是一种治疗乙型肝炎的单克隆抗体方法，是在Vir报告使用单独的siRNA方法VIR-2218的临床数据后的9个月（Vir参加2020年4月16日的乙肝竞赛）。

瞎了

VIR-3434的研究仍然是盲目的，因此昨天Vir披露的任何内容是否相关仍有待辩论。

具体来说，该公司表示，到目前为止，随机分组的八名受试者中有六名的HBsAg平均日剂量减少了1.3 log10 IU / ml，这被认为是该病毒用于复制的四个主要Hep B转录产物之一的表面抗原和反弹。

巧合的是，到目前为止，有6名患者被分配给VIR-3434，有2名患者被分配给安慰剂，因此有力的暗示是，这6名患者与实现HBsAg下降的6名患者相同。但是，绝对没有证据表明是这种情况，因为审判尚未进行。

至少，在考虑HBsAg是否是相关的生物标志物以及甚至主要发生在发展中国家的慢性乙型肝炎是否是可行的市场之前，投资者应该等待查看其他两个受试者的HBsAg水平。为了实现功能性治愈，必须同时抑制病毒DNA和HBsAg，以防止反弹，并且该病毒还存在于cccDNA的库中。

关联？

至于在VIR-3434试验中第八天HBsAg降低的相关性，根据Clinicaltrials.gov，该研究中列出的16个次要终点中的最后一个涉及在第1天至280天之间从基线开始的最大血清HBsAg降低。

但是，Vir昨天似乎报告的全部数据是，随着时间的流逝，八个受试者中每个水平的盲目，混合数据点均出现了六个最令人印象深刻的HBsAg下降，取平均值即可求出平均值。

确实，该公司表示，临床前数据使人们相信，要达到六名选定受试者报告的HBsAg击倒水平，可能需要比目前测试的6mg高得多的VIR-3434剂量。

但是，在不特别知道接受VIR-3434的患者相对于安慰剂患者的情况下，这些最初发现似乎毫无意义。买者自负。

newchinabok

英文看懂了，这个中文真心没看懂

windu

三明治疗法出现曙光